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By Tim
Batchelder for Townsend Letter for Doctors
and Patients
Obesity and diabetes are two of the most prevalent health
conditions in industrial nations.
Yet, despite billions of dollars in research and countless
diets, drugs and therapies, rates of these disorders continue to soar.
Perhaps what is needed is not more investigation into the molecular basis
of these disorders but greater attention to the environmental conditions
that allow expression of them. This is precisely the tact taken by evolutionary
biologists and anthropologists who study health.
From this perspective our craving for fat and sugar
and desire for sedentary lifestyles are natural: in our evolutionary environment
it was precisely these factors that were most rare. The solution, then,
to these diseases of civilization is to recreate this evolutionary environment
to the greatest extent possible, an approach that can be called "culture
engineering" to match the emphasis on genetic engineering found today.
Oversensitive
Insulin Triggers
One of the early pioneers in the application of
genetic knowledge to understanding health conditions was James Neel. In
1962 he published the novel suggestion that the basic defect in type II
or non-insulin-dependent diabetes mellitus (NIDDM) was a quick insulin
trigger. This means that the pancreas secretes insulin too quickly in
response to elevated blood sugar and was an asset to our tribal, hunter-gatherer
ancestors with their intermittent, sometimes feast-or-famine alimentation,
since it should have minimized renal loss of precious glucose. This quick
insulin trigger was under genetic control. Since too quick an insulin
trigger might be as disadvantageous as one that is too slow, it was suggested
that this genetic control might take the form of a balanced polymorphism,
by analogy with the polymorphisms for the sickle cell allele (S) then
receiving so much attention. Recently, two other conditions: essential
hypertension and obesity, have emerged as epidemiologically similar to
NIDDM, being diseases of civilization with gradual onset that have inherited,
familial characteristics.
Fieldwork in Amazonia and Mexico
Neel decided to see whether there was a predisposition
to NIDDM in some tribal groups that surfaced with reservation-style living.
He performed glucose tolerance and other tests on two groups of unacculturated
Amerindians, the Yanomama and Mambo of the Brazilian Amazon Basin. Plasma
glucose, insulin, pancreatic polypeptide, and growth hormone responses
differed somewhat among the two groups but neither of them showed the
large glucose intolerance of the highly acculturated and very obese adult
North American Pima.
To validate Neel's findings authors of another recent
study (Valencia et al 1999) examined NIDDM in Pima Indians of southern
Arizona and the Pima Indians of the Sierra Madre Mountains of northern
Mexico. The Pima Indians are descendents of the Hohokam group that settled
in the valleys of the Gila and Salt rivers in Arizona about 2,000 years
ago. At that time, they used sophisticated agricultural and irrigation
systems together with hunting and gathering to supplement their diet.
At the end of the 19th century, non-Hispanic immigrants diverted their
water supply and, consequently, disrupted their traditional forms of agriculture
which led to many health problems. Government assistance programs and
a cash economy replaced traditional farming activities for the Arizona
Pimas. The Arizona Pimas now have the highest reported
prevalence worldwide of type 2 diabetes, as well as considerable obesity
and other chronic diseases.
In contrast to the Arizona Pimas, Mexican Pima living
in the Sierra Madre mountains live at 1600 m above sea level and practice
traditional, non-mechanized agriculture. They cultivate corn, beans (Phaseolus
vulgaris), and potatoes as their main staples plus a limited amount of
seasonal vegetables and fruits such as zucchini squash, tomatoes, garlic,
green pepper, peaches and apples. They also make heavy use of wild and
medicinal plants in their diet. Their crops are planted on sloped fields
called "maguechis," which are very labor intensive. They also
participate in lumber milling, which is also non-mechanized. There is
no electricity or running water in their homes, and they have to walk
long distances to bring in drinking water or to wash their clothes. They
use no modern household devices; consequently, food preparation and household
chores require extra effort by the women. Based on linguistic similarities
it is estimated that the two Pima groups separated 700 to 1000 years ago.
To study the impact of environmental and genetic
factors on the prevalence of type 2 diabetes and obesity, the researchers
compared 226 Mexican Pimas (120 males and 106 females) with 984 Pimas
(406 males and 578 females) from the Gila River community in Arizona.
A group of 198 unrelated non-Pima individuals (104 males and 94 females)
living in the same environment as the Mexican Pimas were also included
in the study.
Obesity (BMI of 30 or above) was present in only
13% of the Mexican Pimas and 19% of the non-Pima Mexicans, whereas 69%
of the Arizona Pimas met the criterion for obesity. The average difference
in body weight between the Arizona and Mexican Pima men and women was
close to 30 kg.
Physical activity was estimated by the methodology
of Kriska et al., which includes a questionnaire that accounts for the
time spent on various leisure and occupational activities. Mexican Pimas
and non-Mexican Pimas had 23 and 26 hours per week (in the past year)
of occupational physical activity, respectively, whereas Arizona Pimas
had less than 5 hours.
The principal occupational categories for Mexican
Pimas included homemaking, wood milling, nonmechanical farming, and livestock
breeding, as well as complementary activities such as security, construction,
and mining. The principal activities of the Arizona Pimas included homemaking,
mechanical farming, construction, landscape work, equipment or vehicle
operation, and such other activities as security, maintenance, hair styling,
fire fighting, and clerical work.
Diet studies, using the 24-hour recall method,
indicated a fat intake of 26% of total energy intake for the Mexican Pimas,
25% for the non-Pima Mexicans, and 35% for the Arizona Pimas. Cholesterol
intake was 211 mg/day for the Mexican Pimas, 255 mg/day for the non-Pima
Mexicans, and 471 mg/day for the Arizona Pimas. The polyunsaturated to
saturated fat ratios were 1. 1, 0.9, and 0.5 for the same groups, respectively.
Dietary fiber intake was 53 g/day for both Mexican groups and 19 g/day
for the Arizona Pimas.
In sum, the two Mexican groups
lived in an environment which put them at much lower risk for diabetes
and obesity despite a high genetic susceptibility. In contrast,
the Arizona Pima suffer from extremely high rates of these disorders due
to their non-traditional lifestyle.
Laboratory Studies
Based on these field studies scientists have been
busy looking for the "diabetes gene" or a single major locus
that causes NIDDM. Bogardus and Knowler report that in the Pima Indians,
fasting insulin levels yielded evidence for the action of a single major
gene. Mitchell reports that a major (dominant) allele controls insulin
levels during insulin challenge tests in Mexican Americans and this allele
accounts for 35% of changes in 2-hour insulin levels. Recently the entire
human genome was searched for key genes in Mexican Americans with NIDDM
and led to the discovery of a susceptibility locus on chromosome 2, an
allele that accounts for 30% of familial clustering of the disorder.
These studies all fit together nicely with earlier
fieldwork on the Pima when one considers that 31% of Mexican American
genes are descended from Amerindians. Interestingly, unlike Mexican Americans,
smaller samples of non-Hispanic whites and Japanese show no major locus
for NIDDM susceptibility on chromosome 2. Schermacher analyzed Caucasian
families with NIDDM and found a recessive allele controlling fasting insulin
levels that causes about 33% of the difference in fasting insulin levels
in this population.
One stumbling block to a genetic understanding of NIDDM is its supposed
"adult onset". However, studies have shown that children age
1-9 either of whose parents have NIDDM have abnormal glucose tolerance
tests. Children age 5-19 with NIDDM parents also show higher fasting and
2-hour blood insulin levels. They also tend to be obese. All of these
factors are predictors of future NIDDM.
Syndrome X
It's hard not to be excited by
Syndrome X if you are even remotely interested in evolutionary
biology, anthropology and health. Syndrome X is the combination of NIDDM,
hypertension, and a truncal/abdominal
(android) obesity and has also been called insulin
resistance syndrome or the deadly quartet.
To find out whether this syndrome was in fact the
ultimate example of the thrifty genotype in action, Neel took a look at
levels of obesity, hypertension, NIDDM, and combinations of them, in two
adult populations in the United States and in Japan. He found that there
were many females in particular showing the triad. However, he noted that
obesity and hypertension were more closely associated than obesity and
NIDDM. He suggests that Syndrome X is thus not a true syndrome whose elements
share a common (genetic) pathophysiology.
Body Composition
in the Stone Age
One of most interesting recent discoveries in evolutionary
medicine is the radical difference in body composition and lifestyles
of Stone Age versus industrial people. Eaton notes that alimentation was
intermittent in Stone Age humans versus the almost constant consumption
of modern industrial humans. He also notes that while trained athletes
have more muscle mass than early man modern man has much more fat between
muscles, called sarcopenia. Fat and skeletal muscle cells have very different
insulin sensitivities which means that the sensitivity to insulin of skeletal
muscle has been radically changed in the transition to a technological
society. This change wasn't accomplished by an increase in food calories
as much as change in the type of calories consumed and decreased physical
activity.
Total daily energy expenditure in adult members
of hunter-gatherer and traditional agricultural societies is about 3000
kcal/day compared to 2000 or less at present in industrial societies.
In particular, modern industrial use of highly refined carbohydrates,
with the resulting almost instantaneous "sugar highs," has altered
our body's blood sugar balancing mechanisms drastically. This I might
add is a major flaw in the various high protein, low carbohydrate diets
being suggested at present: Stone Age humans did not consume large amounts
of wild animal food, but rather primarily foraged for plant foods. The
difference is not in protein intake (which is more than adequate in modern
industrial diets) but rather the form and type of carbohydrate being consumed:
refined, domesticated plant based versus complex, high fiber, wild plant
based. There has been a parallel genetic evolution in the plant kingdom
to match our dietary habits.
Hypertension and
Obesity
Hypertension and obesity like NIDDM are diseases
of civilization whose prevalence has skyrocketed with industrialization
and are not usually found in hunter gatherers and low energy agriculturalists.
The prevalence of hypertension and obesity in the U.S. is now 40% of adults.
While some monogenically inherited forms of hypertension and obesity are
known they are primarily multifactorial or polygenic. As with NIDDM a
good indicator that these are genetic conditions is the occurrence of
minor abnormalities early in life. Offspring of hypertensives show borderline
hypertension and abnormal red blood cell sodium markers. Likewise, chubby
children tend to become obese adults. Babies of overweight mothers often
show aggressive feeding style.
Civilization Syndromes
While Neel prefers to avoid the Syndrome X term
since these three diseases are not absolutely related by the same genetic
mechanism, he does favor the creation of a term for a series of syndromes
all related to the thrifty genotype concept. In particular he suggests
the terms "syndromes of impaired genetic homeostasis" or "civilization
syndromes," or the "altered lifestyle syndromes," to which
other diseases may yet be added.
Culture Engineering
Since obesity is closely correlated with NIDDM and
essential hypertension these two diseases will increase in prevalence
as obesity increases. Neel notes that computer games designed specifically
to appeal to kids and great amounts of TV watching are certain to accelerate
the rates of obesity in children, unless a return to a simpler lifestyle
can be accomplished.
Gene therapies such as adjusting the body's production
of the hormone leptin are being investigated. However, Neel points out
that we should be humble in our expectations for gene therapy. The monogenic
disorders for which genetic therapy is feasible represent defects in a
well understood metabolic cascade. By contrast, the multifactorial "diseases
of civilization" represent perturbations of complex systems.
A much more promising and cost-effective approach
to these conditions is what Neel has termed "culture engineering"
to counterbalance the recent emphasis on genetic engineering. Just as
genetic engineering implies a conscious effort to improve the genome,
culture engineering implies a conscious effort to develop in all dimensions
the environment in which the human genome finds its optimal expression.
Eaton et al. have called this the Paleolithic Prescription and it constitutes
a "return," where feasible, to aspects of a Paleolithic lifestyle,
especially those involving diet and physical activity. Eaton and colleagues
suggest much higher dietary fiber content and decrease in refined carbohydrate
foodstuffs, less saturated fat, decreased sodium intake, and increased
intake of micronutrients, either through an increased intake of fruits
and vegetables or dietary supplementation.
Simultaneously, a return to a much higher level
of physical activity must be started. In fact, exercise will most likely
be the foundation of evolutionary approaches to wellness. Previous studies
have shown that in most affluent societies one can get people to do heavy
exercise if it is considered a recreational activity, whereas people will
reject fasting or underfeeding.
Conclusions
Neel advocates for a government based national Paleolithic
Prescription health education campaign that targets both children and
adults. However, I am less certain this is the answer. By consistently
prioritizing genetic engineering and other molecular techniques over cultural
engineering the government has shown it has little interest in cultural
and environmental solutions to our health problems. Fortunately, change
might be much simpler. Though Neel never discusses it, thousands of people
in the U.S. and other industrialized nations are already staging just
such a return. The natural health and environmental movements have spawned
such philosophies as voluntary simplicity and bio-regionalism which involve
recreating a simpler, and evolutionarily more appropriate, lifestyle.
About the Author
Tim Batchelder is a science writer specializing
in medical anthropology and human ecology topics. He has a
B.A. from Hamilton College in linguistic anthropology and
is pursuing further graduate coursework in human biology,
ethnobotany, and ethnomedicine. He can be reached at timbatchelder@altavista.com.
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